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Biomedical subjects

Charles B Stephensen

Publications and source records attributed to Charles B Stephensen.

At least 19 recordsLinked to original sources
PubMed2007

Glutathione, glutathione peroxidase, and selenium status in HIV-positive and HIV-negative adolescents and young adults.

BACKGROUND: Antioxidant nutrient deficiencies may hasten the progression of HIV disease by impairing antioxidant defenses. OBJECTIVE: The objective of the study was to determine whether HIV infection is associated with poor selenium status and low antioxidant protection by glutathione and glutathione peroxidase (GPX). DESIGN: In a cross-sectional study of 365 HIV-positive and HIV-negative adolescents and young adults, we examined the relation of plasma selenium, whole-blood glutathione, and whole-blood GPX to HIV status, disease severity, immune activation, and oxidative damage. RESULTS: Selenium deficiency (plasma selenium < 0.070 microg/mL) was not seen in any subjects, and plasma selenium in 244 HIV-positive subjects (0.120 +/- 0.0013 microg/mL) did not differ significantly (P = 0.071) from that in 121 HIV-negative subjects (0.125 +/- 0.0020 microg/mL) . However, multiple regression analysis after adjustment for covariates showed a significant (P = 0.002) negative association between HIV-associated immune activation (plasma neopterin) and plasma selenium concentrations. GPX activity was highest in HIV-positive subjects taking antiretroviral therapy (median: 14.2; 25th, 75th percentiles: 11.1, 18.7 U/mL; n = 130), intermediate in HIV-positive subjects not taking antiretroviral therapy (11.8; 9.4, 15.1 U/mL; n = 114), and lowest in HIV-negative subjects (10.6; 8.6, 12.7 U/mL; n = 121; P < 0.05 for all comparisons). GPX was also positively associated with malondialdehyde, a marker of oxidative damage. CONCLUSIONS: Subjects had adequate selenium status, although HIV-related immune activation was associated with lower plasma selenium concentrations. GPX activity appears to have been induced by the oxidative stress associated with HIV infection and use of antiretroviral therapy. Thus, young, well-nourished subjects can mount a compensatory antioxidant response to HIV infection.

Adolescent↗
PubMed2006

Lysine deficiency and feed restriction independently alter cationic amino acid transporter expression in chickens (Gallus gallus domesticus).

The effect of a lysine-deficient diet on cationic amino acid transporter (CAT1-3) mRNA expression was determined in broiler chickens. Chicks consumed a lysine-adequate (LA; 1.3% lysine) or lysine-deficient (LD; 0.7% lysine) diet. Pair-fed chicks consumed the LA diet in an amount equal to that consumed by LD chicks during the previous day (PLA). CAT 1-3 mRNA expression in the liver, pectoralis and bursa of LD chicks were lower than that of LA and PLA chicks (P<0.05), and levels were not detectable in LD chick thymus. High affinity CAT mRNA expression in isolated bursacytes was 16-fold higher in LD chicks than that of LA chicks (P<0.001). Thymocyte high affinity CAT mRNA expression was 5-fold lower than that of LA chicks (P<0.05). The summed amount of high affinity CAT-1 and CAT-3 mRNA expression in chicks fed a lysine adequate diet was highly correlated (r2=0.51; P<0.001) to a tissue's growth during a lysine deficiency or feed restriction. In the thymus and bursa of LD chicks, CAT mRNA levels differed between resident lymphocytes and their surrounding tissues. By expressing high affinity CAT isoforms, developing lymphocytes may have a greater ability to obtain lysine than their surrounding tissue during a lysine deficiency.

Actins↗
PubMed2006

Vitamins C and E in adolescents and young adults with HIV infection.

BACKGROUND: Oxidative stress during HIV infection may impair immune function, cause more rapid disease progression, and increase requirements for dietary antioxidants such as vitamins C and E. OBJECTIVES: The study had 2 principal objectives. The first was to ascertain whether HIV infection and immune activation were associated with lower plasma concentrations of ascorbate, urate, and alpha- and gamma-tocopherols and with total antioxidant status (TAS). The second objective was to ascertain whether these antioxidants were associated with protection against oxidative damage. DESIGN: This was a cross-sectional study involving 241 HIV-positive and 115 HIV-negative subjects aged 14-23 y. Subjects were primarily female (76%) and African American (70%), and 21% were Hispanic. RESULTS: Plasma ascorbate was significantly lower, but gamma-tocopherol and TAS were significantly higher in subjects with HIV infection when the analysis was adjusted for dietary intake and sex. Plasma alpha-tocopherol did not differ significantly by HIV status. Plasma gamma-tocopherol also was higher in subjects with oxidative damage than in those without such damage. More than 90% of subjects had adequate plasma concentrations for both ascorbate and alpha-tocopherol, although alpha-tocopherol concentrations were lower than expected on the basis of third National Health and Nutrition Examination Survey data. CONCLUSIONS: Low plasma ascorbate concentrations in HIV-positive subjects suggest that vitamin C requirements are significantly higher in those with HIV infection. Plasma tocopherol concentrations were not depressed by HIV infection and may be maintained by compensatory mechanisms such as the activity of alpha-tocopherol transfer protein.

Adolescent↗
PubMed2006

Vitamin D status in adolescents and young adults with HIV infection.

BACKGROUND: Vitamin D status affects immune function and thus may affect the progress of HIV infection. OBJECTIVES: Our goals were to assess vitamin D intake and status in subjects with HIV infection and in matched control subjects and to determine whether HIV infection was associated with vitamin D insufficiency. DESIGN: Plasma 25-hydroxyvitamin D [25(OH)D] concentrations and vitamin D intake were measured in a cross-sectional study of members of the Reaching for Excellence in Adolescent Health (REACH) cohort. RESULTS: The subjects were aged 14-23 y; 74% were female, and 72% were black. Mean (+/-SE) vitamin D intake from food was 30% greater (P = 0.023) in HIV-positive subjects (295 +/- 18 IU/d; n = 237) than in HIV-negative subjects (227 +/- 26 IU/d; n = 121). The prevalence of vitamin D supplement use was 29% (104 of 358 subjects) and did not differ significantly by HIV status (P = 0.87). Mean plasma 25(OH)D did not differ significantly (P = 0.62) between the HIV-positive (20.3 +/- 1.1 nmol/L; n = 238) and HIV-negative (19.3 +/- 1.7 nmol/L; n = 121) subjects, nor was HIV status a significant predictor of plasma 25(OH)D when multiple regression analysis was used to adjust for other variables. The prevalence of vitamin D insufficiency [plasma 25(OH)D < or = 37.5 nmol/L] in the subjects was 87% (312 of 359 subjects). CONCLUSIONS: HIV infection did not influence vitamin D status. The prevalence of vitamin D insufficiency in both HIV-positive and HIV-negative REACH subjects was high, perhaps because these disadvantaged, largely urban youth have limited sun exposure.

Adolescent↗
PubMed2005

Retinoid x receptor agonists increase bcl2a1 expression and decrease apoptosis of naive T lymphocytes.

Vitamin A affects many aspects of T lymphocyte development and function. The vitamin A metabolites all-trans- and 9-cis-retinoic acid regulate gene expression by binding to the retinoic acid receptor (RAR), while 9-cis-retinoic acid also binds to the retinoid X receptor (RXR). Naive DO11.10 T lymphocytes expressed mRNA and protein for RAR-alpha, RXR-alpha, and RXR-beta. DNA microarray analysis was used to identify RXR-responsive genes in naive DO11.10 T lymphocytes treated with the RXR agonist AGN194204. A total of 128 genes was differentially expressed, including 16 (15%) involved in cell growth or apoptosis. Among these was Bcl2a1, an antiapoptotic Bcl2 family member. Quantitative real-time PCR analysis confirmed this finding and demonstrated that Bcl2a1 mRNA expression was significantly greater in nonapoptotic than in apoptotic T lymphocytes. The RXR agonist 9-cis-retinoic acid also increased Bcl2a1 expression, although all-trans-retinoic acid and ligands for other RXR partner receptors did not. Treatment with AGN194204 and 9-cis-retinoic acid significantly decreased apoptosis measured by annexin V staining but did not affect expression of Bcl2 and Bcl-xL. Bcl2a1 promoter activity was examined using a luciferase promoter construct. Both AGN194204 and 9-cis-retinoic acid significantly increased luciferase activity. In summary, these data demonstrate that RXR agonists increase Bcl2a1 promoter activity and increase expression of Bcl2a1 in naive T lymphocytes but do not affect Bcl2 and Bcl-xL expression in naive T lymphocytes. Thus, this effect on Bcl2a1 expression may account for the decreased apoptosis seen in naive T lymphocytes treated with RXR agonists.

Alitretinoin↗
PubMed2005

Immune activation and oxidative damage in HIV-positive and HIV-negative adolescents.

In a cross-sectional study involving subjects from the Reaching for Excellence in Adolescent Health cohort, we examined the associations between HIV status, disease severity, immune activation, and oxidative damage. Subjects (265 HIV-positive and 127 HIV-negative) were young (range: 14-23 years of age) and primarily female (75%) and black (67%). Many subjects, particularly female subjects, were overweight or obese. Relatively few HIV-positive subjects had advanced HIV disease (13%), and 54% were taking antiretroviral therapy (ART). The 2 markers of oxidative damage used in this study (plasma malondialdehyde and protein carbonyl concentrations) did not correlate with each other, and neither was higher in HIV-positive subjects than in HIV-negative controls. Increased oxidative damage was seen in association with male gender, cigarette smoking, marijuana use, immune activation (as indicated by activated CD8 T-cell counts and plasma C-reactive protein concentration), and use of ART, however. Plasma ceruloplasmin was associated with decreased oxidative damage in HIV-positive subjects, although this association was not seen in those taking ART.

Adolescent↗
PubMed2005

Plasma cytokines and oxidative damage in HIV-positive and HIV-negative adolescents and young adults: a protective role for IL-10?

HIV infection causes immune activation that leads to oxidative damage. Proinflammatory cytokines may promote such damage and the regulatory cytokine IL-10 may protect against such damage. To examine the relation of these cytokines to oxidative damage, 67 cases of oxidative damage and 67 matched controls were selected from the reaching for excellence in adolescent health (REACH) study. Subjects were young (15-23 years), largely female (76%), HIV-positive (73%) and black (69%). Proinflammatory cytokines were not significantly associated with oxidative damage but plasma IL-10 had a significant, negative association with oxidative damage. This finding is consistent with a protective role for IL-10 in diminishing oxidative damage during immune activation.

Adolescent↗
PubMed2004

Glucose and cationic amino acid transporter expression in growing chickens (Gallus gallus domesticus).

Tissue glucose transporter (GLUT1-3) and cationic amino acid transporter (CAT1-3) mRNA expression was determined in growing broiler chicks posthatch. In two experiments, tissues were either collected on days 1, 3 and 7 or days 1 and 14 posthatch. Heart and liver were the only tissues expressing a GLUT isoform on day 1. All tissues expressed a GLUT isoform on day 7 except for the thymus. Most tissues expressing a CAT isoform on day 1 decreased mRNA levels through day 7 (P<0.05), except for bursa CAT-1 which tended to increase (P=0.05). The thymus and spleen did not express any CAT isoform mRNA until day 7. The liver was the only tissue expressing GLUT-2 mRNA through day 14. On day 14, GLUT-1, CAT-1 and CAT-2 mRNA were differentially expressed across tissues (P<0.05). High-affinity GLUT and CAT mRNA expression was highest in the heart and bursa, respectively (P<0.05). Total CAT mRNA expression was greatest in the bursa (P<0.05). The thymus had the lowest high affinity GLUT and total CAT mRNA expression on day 14 posthatch. Therefore, T lymphocytes within the thymus may be most susceptible to glucose and cationic amino acid supply.

Aging↗
PubMed2004

US youths in the early stages of HIV disease have low intakes of some micronutrients important for optimal immune function.

OBJECTIVE: We examined the association between micronutrient intakes and human immunodeficiency virus (HIV) infection in youths who were at increased nutritional risk because of the demands of growth and disease as well as poor dietary habits. DESIGN: This was a cross-sectional study to collect dietary intake data using the Block Food Frequency Questionnaire (98.2). Anthropometric, biochemical, clinical, and sociodemographic data were available.Subjects/Setting Participants included 264 HIV-infected and 127 HIV-uninfected adolescents and young adults from the Reaching for Excellence in Adolescent Care and Health network, a multisite observational study on HIV progression. Statistical analyses CD4(+) T cells were stratified for HIV-infected youths: >/=500, 200 to 499, and <200 cells/microL. Micronutrient intakes were compared by presence of HIV infection, using two-sample Student's t tests. Categoric analyses used chi(2) test. Generalized linear regression determined predictors of vitamins A, C, and E; iron; and zinc intakes. RESULTS: Almost half (49.0%) of the HIV-infected participants had CD4(+) T cells >/=500 cells/microL. After controlling for other factors, HIV-infected participants with CD4(+) T cells >/=500 had decreased iron intake (P<.05) and tended to be associated with lower intakes of vitamins C and E (P<.10) compared with those with more advanced disease and HIV-uninfected youths. Among those youths with CD4(+) T cells between 200 and 499 cells/microL, a high anxiety score was associated with a sixfold increase in vitamin A intake as compared with those with a low score.Applications/conclusions Given the increased micronutrient requirements, nutrition counseling with HIV-infected youths should focus on early increase of intake of foods rich in micronutrients to improve growth, slow disease progression, and increase survival.

Adolescent↗
PubMed2004

HIV-infected US youth are at high risk of obesity and poor diet quality: a challenge for improving short- and long-term health outcomes.

OBJECTIVE: To examine the relationships among dietary quality, weight status, and human immunodeficiency virus (HIV) infection in US adolescents and young adults. DESIGN: This cross-sectional study was embedded in the Reaching for Excellence in Adolescent Care and Health cohort study of HIV-infected and HIV-uninfected, at-risk youth. Biochemical, clinical, and sociodemographic data were available. Dietary intake was collected using the Block Food Frequency Questionnaire and a modified Healthy Eating Index was calculated to measure diet quality. SUBJECTS/SETTING: Participants included 264 HIV-infected and 127 HIV-uninfected youth 13 to 23 years old (75.2% women, 67.3% African American/non-Hispanic, 20.5% Hispanic, 12.3% other) at 14 clinic sites. STATISTICAL ANALYSES PERFORMED: Determinants of obesity and the modified Healthy Eating Index were tested using logistic and generalized linear regression. RESULTS: About half (51.7%) of participants were overweight or obese. Obesity was positively associated with being a woman, living independently, watching television >or=3 hours per day, previous dieting, and being from the northeastern or southern United States. Youth who were HIV uninfected or HIV infected with CD4 + T cells >or=500 cells/microL had similar obesity rates; overweight (25%) and obesity (20%) was prevalent among women even with CD4 + T cells <200 cells/microL. The modified Healthy Eating Index score was 56.2+/-0.6, reflecting a diet needing improvement. HIV infection, watching television >or=3 hours/day, and being from the Chicago, IL, area were associated with a lower-quality diet. CONCLUSIONS: Obesity is a common nutrition problem for both HIV-infected and uninfected youth; however, HIV-infected youth are at increased risk of developing metabolic abnormalities. Culturally appropriate, client-focused nutrition education will help youth improve their diet and increase physical activity to reduce health consequences associated with both obesity and HIV infection.

Adolescent↗
PubMed2004

Vitamin A deficiency increases the in vivo development of IL-10-positive Th2 cells and decreases development of Th1 cells in mice.

Vitamin A deficiency impairs both T helper type 1 (Th1)- and type 2 (Th2)-mediated immune responses, although Th2 responses seem to be principally affected. Multiple mechanisms are involved in this immune suppression, but the hypothesis that deficiency affects development of Th1/Th2 memory cell phenotype has not been tested directly in vivo. To do so, lymphocytes from DO11.10 T cell receptor (TCR)-transgenic mice were transferred to vitamin A-deficient or control BALB/c recipients. Recipients were then immunized with the cognate peptide antigen for the TCR-transgenic DO11.10 T cells (OVA(323-339)). After 2-5 wk, the transferred OVA(323-339)-specific T cells were identified from draining lymph nodes with the TCR-clonotypic antibody KJ1-26, and their Th1/Th2 phenotype was characterized by intracellular cytokine staining after in vitro stimulation with phorbol myristate acetate and ionomycin. The percentage of CD4(+)KJ1-26(+) cells positive for IL-10 was 100% greater in vitamin A-deficient mice (3.49 +/- 0.41%; mean +/- SE) than in control mice (1.74 +/- 0.37%). IL-4 did not differ between groups. In addition, the percentages of CD4(+)KJ1-26(+) cells from vitamin A-deficient mice that were positive for interferon (IFN)-gamma (8.8 +/- 0.73%) and interleukin (IL)-2 (39.5 +/- 3.1%) were both lower than the percentages in control mice (11.4 +/- 0.67 and 47.0 +/- 2.8%, respectively). Thus vitamin A deficiency, at the time of initial antigen exposure, enhances the development of IL-10-producing Th2 or T regulatory cells and diminishes the development of Th1 memory cells.

Animals↗
PubMed2003

Moderate antioxidant supplementation has no effect on biomarkers of oxidant damage in healthy men with low fruit and vegetable intakes.

The link between high fruit/vegetable intake and reduced chronic disease may be partly explained by antioxidant protection. To determine the effect of moderate antioxidant intake on biomarkers of oxidant damage, we assessed in vivo lipid and protein oxidation in 77 healthy men whose typical diet contained few fruits and vegetables (mean of 2.6 servings/d). The 39 nonsmokers and 38 smokers, age 20- 51 y, were given a daily supplement (272 mg vitamin C, 31 mg all-rac-alpha-tocopherol, and 400 micro g folic acid), or placebo, for 90 d with their usual diet. Blood and urine were taken at baseline and the end of the study for determination of lipid peroxidation products, including F(2)-total and 8-isoprostanes, and protein carbonyls. Urine thiobarbituric acid reactive substances (TBARS) was the only oxidant damage marker that was significantly higher in smokers compared to nonsmokers (P < 0.05). Supplementation increased plasma ascorbate and tocopherol, but had no effect on the oxidant biomarkers. In healthy young men, the endogenous antioxidant defense system and a modest intake of dietary antioxidants are adequate to minimize levels of in vivo oxidant damage such that they cannot be differentiated by current methods.

Adult↗
PubMed2003

Vitamin A, beta-carotene, and mother-to-child transmission of HIV.

The role of maternal vitamin A supplements in decreasing the risk of mother-to-child HIV transmission has been examined in sub-Saharan Africa. Overall, there is no reduction in either mortality or HIV transmission in two recent studies. Contrary to expectations, one study reported an increased risk of transmission using vitamin A plus beta-carotene supplements.

Adult↗
PubMed2002

Vitamin A enhances in vitro Th2 development via retinoid X receptor pathway.

Vitamin A deficiency diminishes Th2-mediated Ab responses, and high-level dietary vitamin A or treatment with the vitamin A metabolite retinoic acid (RA) enhances such responses. To identify a potential mechanism(s) underlying this in vivo activity of vitamin A, we examined the effects of all-trans and 9-cis RA on development of Th1 and Th2 cell populations using in vitro stimulation of Ag-naive Th0 cells from the DO11.10 TCR-transgenic mouse. Treatment with 9-cis, but not with all-trans RA, at primary stimulation strongly enhanced Th2 development. IL-4-neutralizing Ab blocked this activity, but IL-12- and IFN-gamma-neutralizing Ab did not. Because 9-cis RA regulates gene transcription via either RA receptors or retinoid X receptors (RXRs), we tested the Th2-enhancing activities of the RXR- and RA receptor-selective agonists AGN194204 and 4-((E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid (TTNPB). AGN194204 strongly enhanced Th2 development, whereas TTNPB did not. This RXR agonist also enhanced Th2 development when purified, naive Th0 cells (L-selectin(high)/CD4(+)) were stimulated with CD3 and CD28 Abs in the absence of APCs. During primary antigenic stimulation of naive Th0 cells from DO11.10 mice, AGN194204 increased IL-4 and IL-5 production, decreased IFN-gamma production, increased mRNA in responding T cells for genes involved in Th2 development (IL-4, GATA-3, and c-maf), and decreased mRNA for genes involved in Th1 development (IFN-gamma, T-bet, and IL-12R). These data show that stimulation of the RXR pathway enhances Th2 development, perhaps by affecting the relative expression of pertinent transcription factors, cytokines, and cytokine receptors.

Alitretinoin↗
PubMed2002

Assessment of vitamin A status with the relative-dose-response test in Peruvian children recovering from pneumonia.

BACKGROUND: The relative-dose-response (RDR) test is used to identify subjects with marginal liver vitamin A stores, but its use has not been evaluated during episodes of infection. OBJECTIVE: The objective was to assess, with the RDR test, the vitamin A status of children recovering from pneumonia. DESIGN: As part of a double-blind, placebo-controlled clinical trial of high-dose vitamin A supplements among children hospitalized with pneumonia in Lima, Peru, we examined the association of treatment group, nutritional status, severity of disease, and induction of the acute phase response [on the basis of serum C-reactive protein (CRP)] on serum retinol and the RDR test. RESULTS: Serum retinol was low at admission and increased significantly in both the vitamin A and placebo groups during recovery. Serum CRP had a significant, inverse association with retinol at both admission and discharge. Serum retinol and CRP concentrations never differed significantly between the treatment groups. Among subjects with CRP > or =10 mg/L, 21% in the vitamin A group and 20% in the placebo groups (P = 0.83) had a positive RDR test result. Among subjects with CRP <10 mg/L, 56% in the placebo group but only 6% in the vitamin A group had positive RDR test results (P = 0.002). CONCLUSION: The RDR test was useful in assessing the vitamin A status of children recovering from pneumonia when CRP concentrations were <10 mg/L but not when CRP concentrations were higher.

Anti-Bacterial Agents↗